Abstract
Simple SummaryImmuno-oncology has redefined the treatment of lung cancer, with the ultimate goal being the reactivation of the anti-tumor immune response. This has led to the development of several therapeutic strategies focused in this direction. However, a high percentage of lung cancer patients do not respond to these therapies or their responses are transient. Here, we summarized the impact of immunotherapy on lung cancer patients in the latest clinical trials conducted on this disease. As well as the mechanisms of primary and acquired resistance to immunotherapy in this disease.After several decades without maintained responses or long-term survival of patients with lung cancer, novel therapies have emerged as a hopeful milestone in this research field. The appearance of immunotherapy, especially immune checkpoint inhibitors, has improved both the overall survival and quality of life of patients, many of whom are diagnosed late when classical treatments are ineffective. Despite these unprecedented results, a high percentage of patients do not respond initially to treatment or relapse after a period of response. This is due to resistance mechanisms, which require understanding in order to prevent them and develop strategies to overcome them and increase the number of patients who can benefit from immunotherapy. This review highlights the current knowledge of the mechanisms and their involvement in resistance to immunotherapy in lung cancer, such as aberrations in tumor neoantigen burden, effector T-cell infiltration in the tumor microenvironment (TME), epigenetic modulation, the transcriptional signature, signaling pathways, T-cell exhaustion, and the microbiome. Further research dissecting intratumor and host heterogeneity is necessary to provide answers regarding the immunotherapy response and develop more effective treatments for lung cancer.
Highlights
Lung cancer is the most common cancer, contributing 11.6% of the total case number, and is responsible for 18.4% of cancer-related deaths around the world [1,2]
Between the main histological subtypes of non-small cell lung cancer (NSCLC), studies have shown that SCC tends to arise centrally within the main or lobar bronchus, showing slow growth, and its prevalence is highly associated with tobacco smoking, which increases the mutational burden by 10 times [9]
Immunotherapy has had a deep impact on the treatment paradigm for patients with lung cancer, especially with antibody-based immunotherapy
Summary
Lung cancer is the most common cancer, contributing 11.6% of the total case number, and is responsible for 18.4% of cancer-related deaths around the world [1,2]. Tobacco smoking is the leading risk factor associated with this disease, with 80% of cases attributed to it in Western countries This pattern shows up to 20-fold variation in lung cancer rates from one country to another, especially according to the level of development and socioeconomic status of the region, where the rates of pollution play an important role [5]. Between the main histological subtypes of NSCLC, studies have shown that SCC tends to arise centrally within the main or lobar bronchus, showing slow growth, and its prevalence is highly associated with tobacco smoking, which increases the mutational burden by 10 times [9] In these tumors, the proposed actionable genes with clinical efficacy are limited. The implementation of genetic characteristics for the histological classification of cancer opens the possibility of developing novel targeted therapies and optimizing precision medicine [11]
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